Project description:BackgroundWe assessed the impact of water, sanitation, and hygiene (WASH) and infant and young child feeding (IYCF) interventions on enteric infections in the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial in rural Zimbabwe.MethodsWe tested stool samples collected at 1, 3, 6, and 12 months of age and during diarrhea using quantitative molecular diagnostics for 29 pathogens. We estimated the effects of the WASH, IYCF, and combined WASH + IYCF interventions on individual enteropathogen prevalence and quantity, total numbers of pathogens detected, and incidence of pathogen-attributable diarrhea.ResultsWASH interventions decreased the number of parasites detected (difference in number compared to non-WASH arms, -0.07 [95% confidence interval, -.14 to -.02]), but had no statistically significant effects on bacteria, viruses, or the prevalence and quantity of individual enteropathogens after accounting for multiple comparisons. IYCF interventions had no significant effects on individual or total enteropathogens. Neither intervention had significant effects on pathogen-attributable diarrhea.ConclusionsThe WASH interventions implemented in SHINE (improved pit latrine, hand-washing stations, liquid soap, point-of-use water chlorination, and clean play space) did not prevent enteric infections. Transformative WASH interventions are needed that are more efficacious in interrupting fecal-oral microbial transmission in children living in highly contaminated environments.
Project description:A regulated stress response is essential for healthy child growth and development trajectories. We conducted a cluster-randomized trial in rural Bangladesh (funded by the Bill & Melinda Gates Foundation, ClinicalTrials.gov NCT01590095) to assess the effects of an integrated nutritional, water, sanitation, and handwashing intervention on child health. We previously reported on the primary outcomes of the trial, linear growth and caregiver-reported diarrhea. Here, we assessed additional prespecified outcomes: physiological stress response, oxidative stress, and DNA methylation (N = 759, ages 1-2 years). Eight neighboring pregnant women were grouped into a study cluster. Eight geographically adjacent clusters were block-randomized into the control or the combined nutrition, water, sanitation, and handwashing (N+WSH) intervention group (receiving nutritional counseling and lipid-based nutrient supplements, chlorinated drinking water, upgraded sanitation, and handwashing with soap). Participants and data collectors were not masked, but analyses were masked. There were 358 children (68 clusters) in the control group and 401 children (63 clusters) in the intervention group. We measured four F2-isoprostanes isomers (iPF(2α)-III; 2,3-dinor-iPF(2α)-III; iPF(2α)-VI; 8,12-iso-iPF(2α)-VI), salivary alpha-amylase and cortisol, and methylation of the glucocorticoid receptor (NR3C1) exon 1F promoter including the NGFI-A binding site. Compared with control, the N+WSH group had lower concentrations of F2-isoprostanes isomers (differences ranging from -0.16 to -0.19 log ng/mg of creatinine, P<0.01), elevated post-stressor cortisol (0.24 log µg/dl; P<0.01), higher cortisol residualized gain scores (0.06 µg/dl; P=0.023), and decreased methylation of the NGFI-A binding site (-0.04; P=0.037). The N+WSH intervention enhanced adaptive responses of the physiological stress system in early childhood.
Project description:Wash'Em is a process that supports humanitarians in assessing and designing rapid but context-specific hygiene programmes in crises or outbreaks. The process consists of training implementers, using tools to learn from populations, and entering findings into a software which generates contextualised activities. A process evaluation of Wash'Em use was conducted in a drought-affected area in Midland province, Zimbabwe. Data were collected during the programme design and following implementation using a mix of qualitative methods. Findings were classified against the intended stages of Wash'Em, and the evaluation domains were defined by the UKRI Medical Research Council. The Wash'Em process was not fully implemented as intended. An abridged training was utilised, some of the tools for learning from populations were omitted, many of the recommended activities were not implemented, the delivery modalities were different from intended, the budget available was minimal, and the number of people exposed to activities were fewer than hoped. Despite these 'on the ground' challenges and adaptations, the Wash'Em process was considered feasible by implementers and was seen to be less top-down than most programme design approaches. The populations exposed to the intervention found the activities engaging, understood the content, and reportedly took action to improve handwashing behaviour. Programmes such as Wash'Em, which facilitate community participation and are underpinned by theory and evidence, are likely to yield positive results even if processes are followed imperfectly.
Project description:BackgroundColocalization is a statistical method used in genetics to determine whether the same variant is causal for multiple phenotypes, for example, complex traits and gene expression. It provides stronger mechanistic evidence than shared significance, which can be produced through separate causal variants in linkage disequilibrium. Current colocalization methods require full summary statistics for both traits, limiting their use with the majority of reported GWAS associations (e.g. GWAS Catalog). We propose a new approximation to the popular coloc method that can be applied when limited summary statistics are available. Our method (POint EstiMation of Colocalization, POEMColoc) imputes missing summary statistics for one or both traits using LD structure in a reference panel, and performs colocalization using the imputed summary statistics.ResultsWe evaluate the performance of POEMColoc using real (UK Biobank phenotypes and GTEx eQTL) and simulated datasets. We show good correlation between posterior probabilities of colocalization computed from imputed and observed datasets and similar accuracy in simulation. We evaluate scenarios that might reduce performance and show that multiple independent causal variants in a region and imputation from a limited subset of typed variants have a larger effect while mismatched ancestry in the reference panel has a modest effect. Further, we find that POEMColoc is a better approximation of coloc when the imputed association statistics are from a well powered study (e.g., relatively larger sample size or effect size). Applying POEMColoc to estimate colocalization of GWAS Catalog entries and GTEx eQTL, we find evidence for colocalization of 150,000 trait-gene-tissue triplets.ConclusionsWe find that colocalization analysis performed with full summary statistics can be closely approximated when only the summary statistics of the top SNP are available for one or both traits. When applied to the full GWAS Catalog and GTEx eQTL, we find that colocalized trait-gene pairs are enriched in tissues relevant to disease etiology and for matches to approved drug mechanisms. POEMColoc R package is available at https://github.com/AbbVie-ComputationalGenomics/POEMColoc .
Project description:Case-area targeted interventions (CATIs) against cholera are conducted by rapid response teams, and may include various activities like water, sanitation, hygiene measures. However, their real-world effectiveness has never been established. We conducted a retrospective observational study in 2015-2017 in the Centre department of Haiti. Using cholera cases, stool cultures and CATI records, we identified 238 outbreaks that were responded to. After adjusting for potential confounders, we found that a prompt response could reduce the number of accumulated cases by 76% (95% confidence interval, 59 to 86) and the outbreak duration by 61% (41 to 75) when compared to a delayed response. An intense response could reduce the number of accumulated cases by 59% (11 to 81) and the outbreak duration by 73% (49 to 86) when compared to a weaker response. These results suggest that prompt and repeated CATIs were significantly effective at mitigating and shortening cholera outbreaks in Haiti.
Project description:Coronavirus disease 2019 (COVID-19) is an infectious disease of humans caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the first case was identified in China in December 2019 the disease has spread worldwide, leading to an ongoing pandemic. In this article, we present an agent-based model of COVID-19 in Luxembourg, and use it to estimate the impact, on cases and deaths, of interventions including testing, contact tracing, lockdown, curfew and vaccination. Our model is based on collation, with agents performing activities and moving between locations accordingly. The model is highly heterogeneous, featuring spatial clustering, over 2000 behavioural types and a 10 minute time resolution. The model is validated against COVID-19 clinical monitoring data collected in Luxembourg in 2020. Our model predicts far fewer cases and deaths than the equivalent equation-based SEIR model. In particular, with R0 = 2.45, the SEIR model infects 87% of the resident population while our agent-based model infects only around 23% of the resident population. Our simulations suggest that testing and contract tracing reduce cases substantially, but are less effective at reducing deaths. Lockdowns are very effective although costly, while the impact of an 11pm-6am curfew is relatively small. When vaccinating against a future outbreak, our results suggest that herd immunity can be achieved at relatively low coverage, with substantial levels of protection achieved with only 30% of the population fully immune. When vaccinating in the midst of an outbreak, the challenge is more difficult. In this context, we investigate the impact of vaccine efficacy, capacity, hesitancy and strategy. We conclude that, short of a permanent lockdown, vaccination is by far the most effective way to suppress and ultimately control the spread of COVID-19.
Project description:To calculate the effect of using two different sets of disability weights for estimates of disability-adjusted life-years (DALYs) averted by interventions delivered in one hospital in India.DALYs averted by surgical and non-surgical interventions were estimated for 3445 patients who were admitted to a 106-bed private hospital in a semi-urban area of northern India in 2012-2013. Disability weights were taken from global burden of disease (GBD) studies. We used the GBD 1990 disability weights and then repeated all of our calculations using the corresponding GBD 2010 weights. DALYs averted were estimated for surgical and non-surgical interventions using disability weight, risk of death and/or disability, and effectiveness of treatment.The disability weights assigned in the GBD 1990 study to the sequelae of conditions such as cataract, cancer and injuries were substantially different to those assigned in the GBD 2010 study. These differences in weights led to large differences in estimates of DALYs averted. For all surgical interventions delivered to this patient cohort, 11 517 DALYs were averted if we used the GDB 1990 weights and 9401 DALYs were averted if we used the GDB 2010 disability weights. For non-surgical interventions 5168 DALYs were averted using the GDB 1990 disability weights and 5537 DALYS were averted using the GDB 2010 disability weights.Estimates of the effectiveness of hospital interventions depend upon the disability weighting used. Researchers and resource allocators need to be very cautious when comparing results from studies that have used different sets of disability weights.
Project description:Tidewater glacial fjords in Alaska provide habitat for some of the largest aggregations of harbor seals (Phoca vitulina), with calved ice serving as platforms for birthing and nursing pups, molting, and resting. These fjords have also been popular destinations for tour ships for more than a century, with dramatic increases in vessel traffic since the 1980s. Seals on ice are known to flush into the water when approached by tour ships, but estimating the exposure to disturbance across populations is difficult. Using aerial transect sampling while simultaneously tracking vessel movements, we estimated the spatial overlap between seals on ice and cruise ships in Disenchantment Bay, Alaska, USA. By integrating previously estimated rates of disturbance as a function of distance with an 'intensity surface' modeled spatially from seal locations in the surveys, we calculated probabilities of seals flushing during three separate ship visits. By combining our estimate of seals flushed with a modeled estimate of the total fjord population, we predict that up to 14% of the seals (up to 11% of pups) hauled out would have flushed into the water, depending on the route taken by ships relative to seal aggregations. Such high potential for broad-scale disturbance by single vessels (when up to 4 ships visit per day) was unexpected and underscores the need to 1) better understand long-term effects of disturbance; 2) regularly monitor populations exposed to high vessel traffic; and 3) develop conservation measures to reduce seal-ship overlap.
Project description:BackgroundNeonatal abstinence syndrome (NAS) incidence has significantly increased in the US in recent years. It is therefore important to develop effective intervention protocols that mitigate the long-term consequences of this condition for the mother, her child, and the community.MethodsWe used Monte Carlo simulation to estimate the impact of four interventions for NAS and their combinations on pregnant women with opioid use disorder. The key outputs were changes in incremental costs from baseline from the Medicaid perspective and from a total systems perspective and effect size changes. Simulation parameters and costs were based on the literature and baseline model validation was performed using Medicaid claims for Indiana.ResultsCompared to baseline, the resulting simulation estimates showed that three interventions significantly decreased Medicaid incremental costs by 8% (mandatory opioid testing (MOT)), 4% (patient navigators), and 3% (peer recovery coaches). The combination of the three interventions reduced Medicaid direct costs by 26%. Reductions were similar for total system incremental costs (ranging from 2 to 24%), though MOT was found to increase costs of overdose death based on productivity loss. NAS case reductions ranged from 1% (capacity change) to 13% (MOT).ConclusionsUsing systems-based modeling, we showed that costs associated with NAS can be significantly reduced. However, effective implementation would require the involvement and coordination of several stakeholders. In addition, careful protocols for MOT should be considered to ensure pregnant women don't forgo prenatal care for fear of punitive consequences.